There is considerable indirect evidence that a pituitary factor other than ACTH participates in the regulation of steroid production inthe adrenal cortex. Recently, it has been shown that a large precursor peptide is present in the pituitary gland which contains the amino acid sequence for ACTH, the lipotropins and the endorphins (Proopiolipomelanocortin, POLMC). Beta-endorphin is the most potent endorphin with regard to its opioid activity. We examined, therefore, the effects of Beta-endorphin (Beta-LPH 61-91) and of several of its N-or C-terminal fragments on steroidogenesis in the in situ perfused adrenal gland of hypophgysectomized dogs. We found that Beta-endorphin selectively stimulates the secretion of aldosterone without affecting that of cortisol, with a potency similar to that of ACTH (Beta-LPH 1-39). Met-enkephalin (Beta-LPH 61-65), Alpha-endorphin (Beta-LPH 61-76) and Gramma-endorphin (Beta-LPH 61-77) had no effect on steroid production. However, Beta-EP-(Beta-LPH 43-91) was active in stimulating aldosterone secretion rate. This indicates that the active core of Beta-endorphine resides in the C-terminal portion of the molecule. The results suggest that Beta-endorphin may play a role in the regulation of adrenal steroidogenesis.